VGP_MABVM
ID VGP_MABVM Reviewed; 681 AA.
AC P35253; Q38L42; Q6T6U0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Envelope glycoprotein;
DE AltName: Full=GP1,2;
DE Short=GP;
DE AltName: Full=Virion spike glycoprotein;
DE Contains:
DE RecName: Full=GP1;
DE Contains:
DE RecName: Full=GP2;
DE Flags: Precursor;
GN Name=GP;
OS Lake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strain
OS Kenya/Musoke/1980)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Marburgvirus.
OX NCBI_TaxID=33727;
OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9407; Rousettus aegyptiacus (Egyptian rousette) (Egyptian fruit bat).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 19-37.
RX PubMed=8437211; DOI=10.1128/jvi.67.3.1203-1210.1993;
RA Will C., Muehlberger E., Linder D., Slenczka W., Klenk H.-D., Feldmann H.;
RT "Marburg virus gene 4 encodes the virion membrane protein, a type I
RT transmembrane glycoprotein.";
RL J. Virol. 67:1203-1210(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA Chain P.S.G., Malfatti S.A., Hajjaj A., Vergez L.M., Do L.H., Smith K.L.,
RA McCready P.M.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M.,
RA Schmaljohn A.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=16379005; DOI=10.1128/jvi.80.2.1038-1043.2006;
RA Enterlein S., Volchkov V., Weik M., Kolesnikova L., Volchkova V.,
RA Klenk H.-D., Muehlberger E.;
RT "Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid
RT protein VP30.";
RL J. Virol. 80:1038-1043(2006).
RN [5]
RP SUBUNIT, AND GLYCOSYLATION.
RX PubMed=2024471; DOI=10.1016/0042-6822(91)90680-a;
RA Feldmann H., Will C., Schikore M., Slenczka W., Klenk H.-D.;
RT "Glycosylation and oligomerization of the spike protein of Marburg virus.";
RL Virology 182:353-356(1991).
RN [6]
RP PALMITOYLATION AT CYS-671 AND CYS-673.
RX PubMed=11831710; DOI=10.1006/viro.1995.1151;
RA Funke C., Becker S., Dartsch H., Klenk H.-D., Muehlberger E.;
RT "Acylation of the Marburg virus glycoprotein.";
RL Virology 208:289-297(1995).
RN [7]
RP GLYCOSYLATION.
RX PubMed=1421752; DOI=10.1093/glycob/2.4.299;
RA Geyer H., Will C., Feldmann H., Klenk H.-D., Geyer R.;
RT "Carbohydrate structure of Marburg virus glycoprotein.";
RL Glycobiology 2:299-312(1992).
RN [8]
RP INTERACTION WITH HUMAN ASIALOGLYCOPROTEIN RECEPTOR.
RX PubMed=7844558; DOI=10.1099/0022-1317-76-2-393;
RA Becker S., Spiess M., Klenk H.-D.;
RT "The asialoglycoprotein receptor is a potential liver-specific receptor for
RT Marburg virus.";
RL J. Gen. Virol. 76:393-399(1995).
RN [9]
RP PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN, AND MUTAGENESIS OF LYS-434
RP AND ARG-435.
RX PubMed=10683320; DOI=10.1006/viro.1999.0110;
RA Volchkov V.E., Volchkova V.A., Stroeher U., Becker S., Dolnik O.,
RA Cieplik M., Garten W., Klenk H.-D., Feldmann H.;
RT "Proteolytic processing of Marburg virus glycoprotein.";
RL Virology 268:1-6(2000).
RN [10]
RP PHOSPHORYLATION.
RX PubMed=12033762; DOI=10.1006/viro.2002.1374;
RA Saenger C., Muehlberger E., Loetfering B., Klenk H.-D., Becker S.;
RT "The Marburg virus surface protein GP is phosphorylated at its
RT ectodomain.";
RL Virology 295:20-29(2002).
RN [11]
RP INTERACTION WITH HUMAN CD209 AND CLEC4M.
RX PubMed=15479853; DOI=10.1128/jvi.78.21.12090-12095.2004;
RA Marzi A., Gramberg T., Simmons G., Moeller P., Rennekamp A.J.,
RA Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B.,
RA Steinkasserer A., Becker S., Bates P., Hofmann H., Poehlmann S.;
RT "DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and
RT the S protein of severe acute respiratory syndrome coronavirus.";
RL J. Virol. 78:12090-12095(2004).
RN [12]
RP FUNCTION.
RX PubMed=17005688; DOI=10.1128/jvi.01157-06;
RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T.,
RA Jones S., Feldmann H., Kawaoka Y.;
RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses.";
RL J. Virol. 80:10109-10116(2006).
RN [13]
RP RECEPTOR-BINDING REGION.
RX PubMed=16595665; DOI=10.1074/jbc.m601796200;
RA Kuhn J.H., Radoshitzky S.R., Guth A.C., Warfield K.L., Li W., Vincent M.J.,
RA Towner J.S., Nichol S.T., Bavari S., Choe H., Aman M.J., Farzan M.;
RT "Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire
RT ebolavirus bind a common receptor.";
RL J. Biol. Chem. 281:15951-15958(2006).
RN [14]
RP TRANSMEMBRANE DOMAIN.
RX PubMed=17267489; DOI=10.1128/jvi.02263-06;
RA Mittler E., Kolesnikova L., Strecker T., Garten W., Becker S.;
RT "Role of the transmembrane domain of marburg virus surface protein GP in
RT assembly of the viral envelope.";
RL J. Virol. 81:3942-3948(2007).
CC -!- FUNCTION: GP1 is responsible for binding to the receptor(s) on target
CC cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as
CC cofactors for virus entry into the host cell. Binding to CD209 and
CC CLEC4M, which are respectively found on dendritic cells (DCs), and on
CC endothelial cells of liver sinusoids and lymph node sinuses, facilitate
CC infection of macrophages and endothelial cells. These interactions not
CC only facilitate virus cell entry, but also allow capture of viral
CC particles by DCs and subsequent transmission to susceptible cells
CC without DCs infection (trans infection) (By similarity). {ECO:0000250}.
CC -!- FUNCTION: GP2 acts as a class I viral fusion protein. Under the current
CC model, the protein has at least 3 conformational states: pre-fusion
CC native state, pre-hairpin intermediate state, and post-fusion hairpin
CC state. During viral and target cell membrane fusion, the coiled coil
CC regions (heptad repeats) assume a trimer-of-hairpins structure,
CC positioning the fusion peptide in close proximity to the C-terminal
CC region of the ectodomain. The formation of this structure appears to
CC drive apposition and subsequent fusion of viral and target cell
CC membranes. Responsible for penetration of the virus into the cell
CC cytoplasm by mediating the fusion of the membrane of the endocytosed
CC virus particle with the endosomal membrane. Low pH in endosomes induces
CC an irreversible conformational change in GP2, releasing the fusion
CC hydrophobic peptide (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homotrimer; each monomer consists of a GP1 and a GP2 subunit
CC linked by disulfide bonds. The resulting peplomers (GP1,2) protrude
CC from the virus surface as spikes. GP1,2 interacts with human CD209 and
CC CLEC4M (collectively referred to as DC-SIGN(R)). Asialoglycoprotein
CC receptor (ASGP-R) may be a liver-specific receptor for GP1,2. Members
CC of the Tyro3 receptor tyrosine kinase family may be cell entry factors
CC interacting with GP1,2. {ECO:0000269|PubMed:15479853,
CC ECO:0000269|PubMed:2024471, ECO:0000269|PubMed:7844558}.
CC -!- SUBCELLULAR LOCATION: [GP2]: Virion membrane
CC {ECO:0000250|UniProtKB:Q05320}; Single-pass type I membrane protein
CC {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:Q05320};
CC Single-pass type I membrane protein {ECO:0000255}. Note=In the cell,
CC localizes to the plasma membrane lipid rafts, which probably represent
CC the assembly and budding site. {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBCELLULAR LOCATION: [GP1]: Virion membrane
CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05320}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05320}. Note=GP1 is not anchored to the viral
CC envelope, but forms a disulfid-linked complex with the extravirion
CC surface GP2. In the cell, both GP1 and GP2 localize to the plasma
CC membrane lipid rafts, which probably represent the assembly and budding
CC site. GP1 can also be shed after proteolytic processing.
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- DOMAIN: The coiled coil regions play a role in oligomerization and
CC fusion activity. {ECO:0000250}.
CC -!- DOMAIN: The transmembrane domain is essential and sufficient for
CC recruitment envelope glycoproteins into VP40-enriched multivesicular
CC bodies.
CC -!- PTM: N-glycosylated.
CC -!- PTM: O-glycosylated in the mucin-like region. {ECO:0000305}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The
CC precursor is processed into GP1 and GP2 by host cell furin in the trans
CC Golgi, and maybe by other host proteases, to yield the mature GP1 and
CC GP2 proteins. The cleavage site corresponds to the furin optimal
CC cleavage sequence [KR]-X-[KR]-R. {ECO:0000269|PubMed:10683320}.
CC -!- PTM: GP1 is phosphorylated on serine residues between residues 260 and
CC 273. {ECO:0000269|PubMed:12033762}.
CC -!- MISCELLANEOUS: Filoviruses entry requires functional lipid rafts at the
CC host cell surface. {ECO:0000250}.
CC -!- MISCELLANEOUS: Essential for infectivity, as it is the sole viral
CC protein expressed at the virion surface. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the filoviruses glycoprotein family.
CC {ECO:0000305}.
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DR EMBL; Z12132; CAA78117.1; -; mRNA.
DR EMBL; AY430365; AAR85463.1; -; Genomic_RNA.
DR EMBL; AY430366; AAR85456.1; -; Genomic_RNA.
DR EMBL; DQ217792; ABA87127.1; -; Genomic_RNA.
DR PIR; A45705; A45705.
DR RefSeq; YP_001531156.1; NC_001608.3.
DR SMR; P35253; -.
DR GlyConnect; 579; 7 N-Linked glycans, 5 O-Linked glycans.
DR GeneID; 920945; -.
DR KEGG; vg:920945; -.
DR Proteomes; UP000007771; Genome.
DR Proteomes; UP000137266; Genome.
DR Proteomes; UP000160614; Genome.
DR Proteomes; UP000180448; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR InterPro; IPR014625; GPC_FiloV.
DR InterPro; IPR002561; GPC_filovir-type_extra_dom.
DR Pfam; PF01611; Filo_glycop; 1.
DR PIRSF; PIRSF036874; GPC_FiloV; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host membrane; Host-virus interaction; Lipoprotein;
KW Membrane; Palmitate; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:8437211"
FT CHAIN 19..681
FT /note="Envelope glycoprotein"
FT /id="PRO_0000037515"
FT CHAIN 33..435
FT /note="GP1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000314979"
FT CHAIN 436..681
FT /note="GP2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000314980"
FT TOPO_DOM 19..648
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 649..669
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 670..681
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 38..188
FT /note="Receptor-binding"
FT REGION 223..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..455
FT /note="Mucin-like region"
FT /evidence="ECO:0000250"
FT REGION 529..549
FT /note="Fusion peptide"
FT /evidence="ECO:0000250"
FT COMPBIAS 242..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..427
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 435..436
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT LIPID 671
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000305|PubMed:11831710"
FT LIPID 673
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000305|PubMed:11831710"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 487
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 37..610
FT /note="Interchain (between GP1 and GP2 chains)"
FT /evidence="ECO:0000250"
FT DISULFID 92..119
FT /evidence="ECO:0000255"
FT DISULFID 211..226
FT /evidence="ECO:0000255"
FT DISULFID 512..557
FT /evidence="ECO:0000255"
FT DISULFID 602..609
FT /evidence="ECO:0000250"
FT VARIANT 547
FT /note="V -> G (in strain: pp3/guinea pig lethal and pp4/
FT guinea pig nonlethal)"
FT MUTAGEN 434
FT /note="K->M: Partial loss of cleavage between GP1 and GP2."
FT /evidence="ECO:0000269|PubMed:10683320"
FT MUTAGEN 435
FT /note="R->L: Complete loss of cleavage between GP1 and
FT GP2."
FT /evidence="ECO:0000269|PubMed:10683320"
SQ SEQUENCE 681 AA; 74376 MW; CC89305C64D34B0B CRC64;
MKTTCFLISL ILIQGTKNLP ILEIASNNQP QNVDSVCSGT LQKTEDVHLM GFTLSGQKVA
DSPLEASKRW AFRTGVPPKN VEYTEGEEAK TCYNISVTDP SGKSLLLDPP TNIRDYPKCK
TIHHIQGQNP HAQGIALHLW GAFFLYDRIA STTMYRGKVF TEGNIAAMIV NKTVHKMIFS
RQGQGYRHMN LTSTNKYWTS SNGTQTNDTG CFGALQEYNS TKNQTCAPSK IPPPLPTARP
EIKLTSTPTD ATKLNTTDPS SDDEDLATSG SGSGEREPHT TSDAVTKQGL SSTMPPTPSP
QPSTPQQGGN NTNHSQDAVT ELDKNNTTAQ PSMPPHNTTT ISTNNTSKHN FSTLSAPLQN
TTNDNTQSTI TENEQTSAPS ITTLPPTGNP TTAKSTSSKK GPATTAPNTT NEHFTSPPPT
PSSTAQHLVY FRRKRSILWR EGDMFPFLDG LINAPIDFDP VPNTKTIFDE SSSSGASAEE
DQHASPNISL TLSYFPNINE NTAYSGENEN DCDAELRIWS VQEDDLAAGL SWIPFFGPGI
EGLYTAVLIK NQNNLVCRLR RLANQTAKSL ELLLRVTTEE RTFSLINRHA IDFLLTRWGG
TCKVLGPDCC IGIEDLSKNI SEQIDQIKKD EQKEGTGWGL GGKWWTSDWG VLTNLGILLL
LSIAVLIALS CICRIFTKYI G
